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Aging Cell. 2016 Feb;15(1):149-54. doi: 10.1111/acel.12421. Epub 2015 Nov 17.

DNA methylation age is associated with mortality in a longitudinal Danish twin study.

Author information

The Danish Aging Research Center, and The Danish twin Registry, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
Max Planck Odense Center on the Biodemography of Aging, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
Max Planck Institute for Demographic Research, Rostock, Germany.
The Center for Human Development and Aging, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA.
Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.


An epigenetic profile defining the DNA methylation age (DNAm age) of an individual has been suggested to be a biomarker of aging, and thus possibly providing a tool for assessment of health and mortality. In this study, we estimated the DNAm age of 378 Danish twins, age 30-82 years, and furthermore included a 10-year longitudinal study of the 86 oldest-old twins (mean age of 86.1 at follow-up), which subsequently were followed for mortality for 8 years. We found that the DNAm age is highly correlated with chronological age across all age groups (r = 0.97), but that the rate of change of DNAm age decreases with age. The results may in part be explained by selective mortality of those with a high DNAm age. This hypothesis was supported by a classical survival analysis showing a 35% (4-77%) increased mortality risk for each 5-year increase in the DNAm age vs. chronological age. Furthermore, the intrapair twin analysis revealed a more-than-double mortality risk for the DNAm oldest twin compared to the co-twin and a 'dose-response pattern' with the odds of dying first increasing 3.2 (1.05-10.1) times per 5-year DNAm age difference within twin pairs, thus showing a stronger association of DNAm age with mortality in the oldest-old when controlling for familial factors. In conclusion, our results support that DNAm age qualifies as a biomarker of aging.


DNA methylation; biological age; biomarker; epigenetic clock; mortality; twins

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